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Symbol LMNA contributors: mct/ - updated : 28-09-2019
HGNC name lamin A/C
HGNC id 6636
Corresponding disease
CMD1A cardiomyopathy, dilated 1A
CMT2B1 Charcot-Marie-Tooth disease, axonal, type 2B1
EMD2 Emery-Dreifuss muscular dystrophy 2
EMD3 Emery-Dreifuss muscular dystrophy 3
FPLD2 familial partial lipodystrophy
HHSS heart hand syndrome, Slovenian type
LDHCP lipoatrophy with diabetes, hepatic steatosis, hypertrophic cardiomyopathy and leukomelanodermic papules
LGMD1B limb girdle muscular dystrophy 1B
MADYS1 mandibuloacral dysplasia
MCPRS myopathy and cutaneous progeria syndrome
PRO1 Hutchinson-Gilford progeria syndrome
RDMP2 restrictive dermopathy, lethal 2
WRN2 Werner syndrome 2
Location 1q22      Physical location : 156.084.460 - 156.109.878
Synonym name
  • progerin
  • 70 kDa lamin
  • renal carcinoma antigen NY-REN-32
  • lamin A/C-like 1
  • Synonym symbol(s) LMN1, FPL, LDP, LB3T, LMNB3, IDC, CDDC, FPLD, HGPS, LDP1, LMNC, CDCD1
    TYPE functioning gene
    STRUCTURE 25.42 kb     12 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box) (TATA box)
    text structure
  • binding sites for SREBF1, SREBF2
  • a retinoic acid-responsive element in the LMNA promoter that is regulated by the transcription factors c-Jun and Sp1/Sp3
  • also other regulatory motifs in the LMNA promoter binding the transcription factors Sp1/3, c-Jun, and c-Fos, and the transcriptional coactivator CREB-binding protein
  • MAPPING cloned Y linked N status confirmed
    Map cen - D1S3757 - [D1S2346 - D1S2715 - NPR1 - DAP3 - D1S303 - D1S2777 - SCAMP3 - MUC1 - D1S2714 - D1S2140 - LMNA - D1S2721 - D1S2624 ] - D1S506 - INSRR - FGFR2 - qter
    Authors Shackleton (00)
    Text [FPL ]
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 3243 74.1 664 - 2008 18381888
  • lamin A, or variant 1 isoform 1
  • associates with chromatin both directly and indirectly and has been suggested to play important roles in chromatin organization, transcription, DNA replication, and apoptosis
  • SUMO1 modification of the lamin A tail targets at least two AAs: highly predicted residue K420 and totally unexpected residue K486
  • 10 splicing 2077 65.2 572 - 2008 18381888
  • lamin C or variant 2 Isoform 2
  • an alternative splice site in the 3' coding region resulting in a distinct C terminus
  • lamin C AAs 1–566 are identical to lamin A, suggesting that lamin C might also be modified by SUMO1
  • 11 splicing 3153 70.8 634 - 2008 18381888
  • lamin Adelta10 isoform, or variant 3 isoform 3
  • lacking an interval sequence
  • - - 2257 - 614 - 2007 17360355
  • progerin/LADelta50
  • 50-AA deletion within its C terminus (deletion from the C-terminal tail, AA 607–656)
  • lacking the normal cleavage site to remove a C-terminal farnesyl group
  • during interphase, irreversibly farnesylated progerin/LADelta50 anchors to the nuclear membrane and causes characteristic nuclear blebbing
  • mislocalizes into insoluble cytoplasmic aggregates and membranes during mitosis and causes abnormal chromosome segregation and binucleation
  • DNA/chromatin binding properties of the progerin tail are distinct from those of wild-type A-type and B-type lamin tails, and has a reduced DNA/chromatin binding capacity and modified trimethylated H3K27 binding pattern (PMID: 20580717)
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Endocrineadrenal gland   highly
    Respiratoryrespiratory tracttrachea  highly
    Skin/Tegumentskin   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
     differentiated cell
    cell lineage
    cell lines
    at STAGE
  • an N terminal globular head domain
  • a central rod domain (alpha-helical rod domain) , responsible for the formation of in-parallel and in-register coiled-coil dimers, the building blocks of lamin polymers
  • a nuclear localization signal (NLS)
  • an Ig fold domain
  • AA stretch (aa 607–646) of lamin A constitutes a binding site for DNA and chromatin
  • a C terminal globular tail domain including a CAAX prenylation motif in prelamin A, cleaved in the lamin A and a DNA binding domain, a signal for posttranslational farnesylation by the farnesyltransferase enzyme
  • conjugated FlavoP
    mono polymer homomer , heteromer , dimer , tetramer
    isoforms Precursor of two alternatively spliced isoforms A et C, converted in mature form LMNA after isoprenylation of CAAX box and incorporation into the lamina structure
    interspecies ortholog to rattus Lmna (85.5pc)
    ortholog to murine Lmna (96.5pc)
    ortholog to zebrafish lmna (76.1pc)
  • intermediate filament family
  • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,cytoplasm,cytoskeleton,intermed filament
    intracellular,nuclear envelope,int
    intracellular,nuclear envelope,lamina
  • nuclear matrix, constituent of the inner nuclear membrane intermediate filament
  • SUN1 and LMNA colocalize at the Nuclear Envelope (NE)
  • detected predominantly in the nuclear rim
  • nuclear periphery proteins LMNA, TMPO and BANF1 relocate to the spindle and the cell cortex in mitosis
  • LMNA interacts with EMD at the inner nuclear membrane
  • basic FUNCTION
  • mediating interactions with the nuclear envelope, and also tethering the nuclear envelope to chromatin
  • playing a major role in chromatin organization, DNA replication and RNA polymerase II-dependent gene expression
  • involved in nuclear stability, chromatin structure and gene expression
  • playing a key role in maintaining cellular resistance to deformation and in nucleo-cytoskeletal integrity
  • involved in the modulation of TGF-beta1 on collagen production, a marker of mesenchymal differentiation via nuclear phosphatases such as PPP2R3B
  • acting as inhibitors of adipocyte differentiation, possibly by affecting PPARgamma2 and insulin signaling
  • invovled in physiological aging
  • playing a critical role through the C-terminal globular lamin A/C region in nuclear structure (major contribution of abnormal assembly to the progeroid phenotype)
  • playing a role in normal cell senescence
  • involved in muscle differentiation
  • link between pre-lamin A processing and heterochromatin remodeling
  • SUMO modification is important for normal LMNA function and implicate an involvement for altered sumoylation in the E203G/E203K lamin A cardiomyopathies
  • importance of lamins in nuclear assembly and chromatin organization, and essential role in establishing and maintaining nuclear architecture
  • might have a role in normal physiological cellular senescence
  • LMNA and LBR sequentially tether peripheral heterochromatin and inversely regulate differentiation
  • type V intermediate filament protein forming a filamentous meshwork, the lamina, underneath the inner nuclear membrane, for nuclear envelope structures organization and interphase chromatin anchoring
  • component of the nuclear lamina that plays a critical role in the structural organization and function of the nucleus
  • is part of the nuclear lamina, a meshwork of intermediate filaments underlying the inner nuclear membrane
  • LMNA, TMPO and BANF1 are assembled into a protein complex during mitosis in order to regulate assembly and positioning of the mitotic spindle
  • LMNA localizes throughout the nucleus, where it associates with the chromatin-binding protein TMPO
  • novel role of nucleoplasmic lamin A/C and TMPO in regulating euchromatin
  • LMNA, LMNB1, LMNB2 not only constitute a scaffold for nuclear shape, rigidity and resistance to stress but also contribute to the organization of chromatin and chromosomal domains
  • CNOT1-LMNA-Hedgehog signaling pathway axis exerts an oncogenic role in osteosarcoma progression
  • remarkable role for LMNA and EMD as modulators of cytoskeletal and chromatin organization in the interphase nucleus
  • LMNA, and EMD modulate subcellular distribution and organization of actin in cells
  • LMNA and EMD modulate KLK10, SMAD2 and BCL2L12 expression levels as well as the spatial positions of gene loci in the interphase nucleus
  • mislocalization of LINC complex proteins (SUN1, SUN2, LMNA, EMD, SYNE1) is a significant characteristic of cellular senescence phenotypes and may influence complex events at the nuclear membrane, including trafficking and heterochromatin attachment
  • CELLULAR PROCESS nucleotide, chromatin organization
    nucleotide, transcription, regulation
    cell organization/biogenesis
    a component
  • constituent of the inner nuclear membrane intermediate filament
  • part of LINC complex
  • TMPO-LMNA complex negatively affects cell proliferation
  • LMNA, EMD are part of a nuclear sub-complex, that partner with Nuclear Myosin 1 (MYO1C) and actin
    small molecule
  • SREBF1 (retention of SREBF1 by LMNA, causing down-regulation of PPARG expression and reducing the rate of preadipocytes differentiation) and SREBF2
  • TRAF3
  • EMD
  • interacting with the nuclear actin
  • interacting with RB, MADH2, PPP2R3B (crucial interaction for proper regulation of mesenchymal cellular physiology)
  • binding to CCND3
  • interacts with D41Z4 (Lamins A/C are involved in the anti-silencing activity of D4Z4 and uncovers the involvement of both CTCF and A-type Lamins in the regulation of an insulator in human cells)
  • molecularly connected with EMD (emerin-prelamin A interplay influences nuclear organization)
  • nucleoporin NUP88 is interacting with nuclear lamin A
  • interacting with MLIP (interaction domain is between AAs 1 and 130 of LMNA, which includes the N-terminal globular head domain plus coil 1A, linker 1, and the first 43 AAs of coil 1B)
  • LMNA splicing regulation by the SR proteins SRSF1 and SRSF6
  • TMEM201 associates with SUN2 and LMNA, and the presence of TMEM201 at the nuclear envelope requires LMNA
  • interaction between accumulated preLMNA and SP1 transcription factor, results in altered extracellular matrix gene expression, impairing adipogenesis
  • SUMO1 is involved in posttranslational modification of the lamin A tail
  • AKT1 regulates LMNA transcription, having a function in the control of prelamin A stability and expression
  • LMNA inhibited TPR import because transport of large protein cargoes was sensitive to changes in the Ran nuclear/cytoplasmic distribution that occurred in PRO1
  • physical interaction between FAM96B and LMNA, which may provide some clues to the mechanisms of LMNA in premature aging, and interaction between the two proteins might give rise to the retention of FAM96B at the nuclear envelope
  • functional association between LMNA and fragile X-related protein 1 (FXR1)
  • LMNA also interacts with euchromatin
  • SUMO1 conjugation of RB1 and LMNA is modulated by the SUMO protease SENP1 and sumoylation of both proteins is required for their interaction
  • CNOT1 interacted with LMNA (lamin A) and functioned as a positive regulator of this intermediate filament protein
  • BANF1 interaction with LMNA plays an essential role, and mutations associated with progeroid syndromes leads to a dysregulation of BANF1-mediated chromatin organization and gene expression
  • LMNA domain both directly binds self-assembled EMD and interacts with monomeric EMD LEM domain through the dimeric BANF1 protein
  • LMNA, and EMD modulate the nuclear localization of MYO1C
  • LMNA is a modulator of MYO1C localization in cells, as it regulates the stability of EMD-MYO1C interactions
  • LMNA and EMD partner to modulate genome organization via their cytoskeletal interactors – actin and MYO1C
  • cell & other
    Phosphorylated by AKT1 (AKT1 phosphorylation at S404 targets the precursor prelamin A for degradation)
    Other disassembly at the start and reassembly at the end of mitosis mediated by phosphorylation, dephosphorylation
    is posttranslationally modified, with the addition of a farnesyl group at the C terminus that seems to assist in “zip-coding” the protein to the inner surface of the nuclear membrane; the protein then needs to be released from this tether, which is accomplished by an enzyme called ZMPSTE24, and the abnormal splice event that gives rise to progerin eliminates the ZMPSTE24 cleavage, so progerin remains permanently farnesylated
    corresponding disease(s) EMD2 , LGMD1B , CMD1A , CMT2B1 , FPLD2 , MADYS1 , PRO1 , WRN2 , RDMP2 , LDHCP , EMD3 , MCPRS , HHSS
    related resource Limb-Girdle Muscular Dystrophy pages
    Mutation Database of Inherited Peripheral Neuropathies
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    by hypermethylation associated with poor outcome in diffuse large B-cell lymphomas
    constitutional germinal mutation      
    results in increased sensitivity to DNA damaging agents, an elevated DNA damage response, and a senescent phenotype
    constitutional       loss of function
    in striated muscle disease mutated proteins are defective in anchoring transmembrane actin-associated nuclear lines for nuclear movement
    tumoral     --low  
    silencing of A-type lamins by DNA methylation in some cancers could contribute to the genomic instability that drives malignancy
    constitutional germinal mutation      
    LMNA mutation should be considered in myopathy patients with inflammatory changes during infancy
    constitutional     --over  
    in osteoarthritis (OA) chondrocytes, and increased nuclear accumulation of LMNA in response to catabolic stress may account for the premature aging phenotype and apoptosis of OA chondrocytes
    constitutional     --low  
    depletion of LMNB1 or LMNA/Cwas sufficient to recapitulate some oncogene-induced senescence (OIS) features, including cell cycle exit and downregulation of nuclear envelope (NE) proteins 7)
  • to subcutaneous abdominal abnormal adipocyte size
  • to metabolic syndrome and also higher mean fasting triglyceride and lower mean HDL-cholesterol concentrations
  • to enhanced longevity
  • Variant & Polymorphism SNP , other
  • 1908 C>T Pima Indians
  • H566H polymorphism associated with metabolic syndrome and also higher mean fasting triglyceride and lower mean HDL-cholesterol concentrations in the Old Order Amish
  • Candidate gene
    Therapy target
    correction of cellular phenotypes of Hutchinson-Gilford Progeria cells by RNA interference, as potential gene therapy
    ERK inhibition as a therapeutic option to prevent or delay heart failure in Emery–Dreifuss muscular dystrophy and related disorders caused by mutations in LMNA
    processing of prelamin A could become a new approach to regulate osteoblastogenesis and bone turnover and thus for the prevention and treatment of senile osteoporosis
    correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site (treatment inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome)
    lamins-deficient tumor cells could represent a good target for radiation therapy
  • abnormal activation of the extracellular signal-regulated kinase (ERK) branch of the mitogen-activated protein kinase (MAPK) signaling cascade in hearts of Lmna H222P ‘knock in’ mice, a model of autosomal Emery–Dreifuss muscular dystrophy
  • changes in the splicing ratio between lamin A and progerin are key factors for lifespan since heterozygous mice harboring the mutation lived longer than homozygous littermates but less than the wild-type
  • Lmna(-/-) mice display multiple tissue defects and die by 6-8 weeks of age reportedly from dilated cardiomyopathy with associated conduction defects